For more than 20 years, researchers have been attempting to apply magnetic resonance imaging (MRI) to the characterization and diagnosis of pulmonary diseases. In part, this is motivated by the ongoing need for non-invasive methods to diagnose and stage interstitial diseases that challenge clinicians. Of particular interest in pulmonary MRI research is the potential to distinguish inflammation from fibrosis regionally and non-invasively. Although this is important for diagnosis and characterization of disease and disease activity, emphasis is often placed on assessing and differentiating patients for appropriate courses of treatment.
The most routinely used modality for thoracic imaging is x-ray computed tomography (CT); however, CT lacks specificity in some situations. This lack of specificity is described in the following publications:
Yi C A, Lee K S, Han J, Chung M P, Chung M J, Shin K M. 3-T MRI for differentiating inflammation- and fibrosis-predominant lesions of usual and nonspecific interstitial pneumonia: comparison study with pathologic correlation. AJR Am J Roentgenol 2008; 190(4): 878-885.
American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002; 165(2):277-304.
Lutterbey G, Grohe C, Gieseke J, et al. Initial experience with lung-MRI at 3.0 T: Comparison with CT and clinical data in the evaluation of interstitial lung disease activity. Eur J Radiol 2007; 61(2):256-261.
Jung J I, Park S H, Lee J M, Hahn S T, Kim K A. MR characteristics of progressive massive fibrosis. J Thorac Imaging 2000; 15(2):144-150.
Because MRI is able to distinguish tissue types, it is a promising imaging modality for disease diagnosis. To date, there have been several studies focused on characterizing and differentiating inflammation and fibrosis using various MRI techniques, such as T1-weighted imaging, T2-weighted imaging, and signal intensity (S0) changes with contrast agent wash-in or wash-out. These studies are described in the following papers:
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Berthezene Y, Vexler V, Kuwatsuru R, et al. Differentiation of alveolitis and pulmonary fibrosis with a macromolecular MR imaging contrast agent. Radiology 1992; 185(1):97-103.
Kersjes W, Hildebrandt G, Cagil H, Schunk K, von Zitzewitz H, Schild H. Differentiation of alveolitis and pulmonary fibrosis in rabbits with magnetic resonance imaging after intrabronchial administration of bleomycin. Invest Radiol 1999; 34(1):13-21.
Yi C A, Lee K S, Han J, Chung M P, Chung M J, Shin K M. 3-T MRI for differentiating inflammation- and fibrosis-predominant lesions of usual and nonspecific interstitial pneumonia: comparison study with pathologic correlation. AJR Am J Roentgenol 2008; 190(4): 878-885.
Jung J I, Park S H, Lee J M, Hahn S T, Kim K A. MR characteristics of progressive massive fibrosis. J Thorac Imaging 2000; 15(2):144-150.
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Karmouty-Quintana H, Cannet C, Zurbruegg S, et al. Bleomycin-induced lung injury assessed noninvasively and in spontaneously breathing rats by proton MRI. J Magn Reson Imaging 2007; 26(4):941-949.
Others have used non-imaging techniques to measure T1, T2, or water diffusion in excised lungs. These studies are described in the following papers:
Cutillo A G, Chan P H, Ailion D C, et al. Characterization of bleomycin lung injury by nuclear magnetic resonance: correlation between NMR relaxation times and lung water and collagen content. Magn Reson Med 2002; 47(2):246-256.
Taylor C R, Sostman H D, Gore J C, Smith G W. Proton relaxation times in bleomycin-induced lung injury. Invest Radiol 1987; 22(8):621-626.
Generally, measurements of T1 and water diffusion have not shown any ability to distinguish inflammation and fibrosis, and measurements of T2 have had mixed results. In the latter case, Taylor et al. reported an increase in T2 with chronic fibrosis and a decrease with inflammation in bleomycin-dosed mice, opposite that in bleomycin-dosed rats reported by Cutillo et al. Results of S0 measurements also show that signal intensity may help distinguish inflammation and fibrosis. However, results were generally based on prior knowledge of dose history or disease state, and the ability to blindly distinguish between inflammation, fibrosis, and admixtures of the two was not demonstrated. There are even conflicting reports of S0 changes. For example, Kersjes et al. showed a significant increase in S0 only three hours after bleomycin exposure in rabbits, while Karmouty-Quintana et al. showed no increase in S0 even after 24 hours in a similar experiment with rats. Although some variation in reported results may be attributed to species-specific differences in bleomycin reactions, the apparent lack of a single parameter or set of parameters that can reliably identify inflammation and fibrosis warrants further investigation.
Accordingly, there exists a need for new methods and techniques that offer improvements over the prior art. The present invention fulfills that need.